During the past year, we have continued to analyze this unique longitudinal prospective study of a cohort of young adults who have been followed for 25 years since the age of 18. We first completed an analysis of the validity of definition of the headache subtypes and examined their prevalence, impact, and stability (Merikangas et al, submitted). Our findings reveal that: (1) the cumulative one-year prevalence of migraine without aura with repeated interviews over a 20-year period is very high (33.5%), whereas that of migraine with aura is far less prevalent, (2.9% across 14 years of follow- up);(2) about 32% of those with migraine continue to experience only migraine over 20 years of follow-up; (3) the longitudinal specificity of headache subtypes is fairly low, with a high prevalence of co-occurrence across headache subtypes and little prospective stability of the specific pure types of headache;and (4) there is a gradient of clinical severity across headache subtypes moving from migraine with aura to migraine without aura, tension-type headache, and unclassified headaches. We also examined the impact of psychiatric comorbidity in migraine, tension-type and other headaches. The findings highlight the importance of prospective follow-up of people with headache. We found that migraine and other headache subtypes were substantially comorbid with mood and anxiety disorders. Comorbid migraine was associated with the highest levels of consulting a physician, treatment-seeking, medication use, distress and impairment. This study provides valuable insight on the association between specific headache subtypes and psychiatric conditions, as well as the differential impact of these subtypes on the affected individual using prospective data from a population-based sample. Understanding the specificity of these associations will aid in our efforts to more accurately detect at-risk individuals, inform the development of more targeted prevention and treatment efforts and help refine studies examining the etiology of these conditions. We also examined the strength of association between smoking and mood disorders and the association between smoking and its traditional risk factors, comparing those who started smoking in adolescence with those who started smoking in early adulthood (Ajdacic-Gross et al). We found that adolescent onset of smoking was associated strongly with later major depression, dysthymia or bipolar disorders and, furthermore, with parental smoking, extroverted personality and discipline problems and rebelliousness in youth. However, only depression and dysthymia were associated with adult onset smoking and other risk factors associated with smoking were not so associated in this group. Our results suggest that more specific study designs are needed to shed more light on adult onset of smoking. The interplay between two subclinical psychosis symptoms dimensions, and one depression symptom dimension, was investigated using this unique longitudinal data (Rossler et al). To summarize, the main driving force within the dynamics between symptoms of psychosis and depression is the schizotypal symptoms subscale, which represents social and interpersonal deficiencies, ideas of reference, suspiciousness, paranoid ideation, and finally, odd behavior. It exercises a strong effect on the depression symptoms, and a moderate effect on the schizophrenia nuclear symptoms subscale. Depression has partly a mediator function in this dynamics. Our findings suggest strongly that schizotypal symptoms preferably convey depression symptoms, which for their part can convey schizophrenia nuclear symptoms. Finally we examined smoking prevalence in association with mental disorders to include not only psychiatric disorders but also subthreshold disorders in the analysis. The association between smoking and mental disorders turned out to be clearly stronger if subthreshold mental disorders were appropriately considered in the analyses. Constructing appropriate reference groups is as crucial for the analysis of mental disorders and their outcomes as constructing adequate diagnostic groups. During the next year, we plan to integrate the results of the latest wave of the study that was just completed, and to evaluated the prevalence, core phenomenology, stability and comorbidity of the atypical subtype of depression and neurasthenia. Public Health Implications These findings have important implications for classification and etiologic studies of migraine and other headaches, as well as for clinical care and health policy. First, our findings clearly demonstrate the high magnitude of disability associated with these headache syndromes across young to middle adulthood. Second, this study highlights the importance of prospective research in studying headache syndromes. Clinical evaluation and treatment of headache necessarily relies on retrospective recall that has been shown to be highly unreliable. Clinicians should attempt to obtain maximal information on the past history rather than relying on the current clinical presentation in treatment decision-making. Third, the longitudinal overlap of headache subtypes has important implications for classification of headache syndromes. One of the major impediments to headache classification is that diagnostic criteria are based on characterization of episodes rather than longitudinal trajectories of headaches within individuals across the lifetime. Etiologic research may benefit from a more descriptive empirical approach that captures the protean manifestations of headache across lifes developmental stages.